1. Field of the Invention
The present invention relates generally to the fields of bone cells and also to isoflavones. Particularly, the invention concerns the discovery that the isoflavone genistein inhibits the acid secretion of bone-degrading cells termed osteoclasts. The invention thus provides methods and compositions for use in inhibiting osteoclast activity, as may be employed to reduce bone resorption.
2. Description of the Related Art
Metabolic bone disease is a common and economically important problem that affects many patients. Bone degradation often leads to osteoporosis, as well as bone lesions in metastatic cancer and other disease states. This degradation is mediated by cells of the osteoclast type. Current therapy for bone resorption is not very effective, which has led to an active pursuit of effective anti-osteoclastic drugs.
Candidate compounds to treat bone resorption include (1) gallium nitrate; (2) a large number of bisphosphonate derivatives; (3) certain antibiotics, such as herbimycin and plicamycin; (4) bone-binding antibiotics, principally tetracyclines; (5) protease inhibitors; (6) estrogen analogues or inhibitors such as raloxifene and tamoxifen; and (7) calcitonin and calcitonin congeners.
Each of the foregoing candidates suffer from independent sets of drawbacks that limit their effectiveness. Most notably perhaps, plicamycin (also known as mithramycin) has been shown to have fatal side effects. Also, gallium nitrate, bisphosphonate derivatives and bone-binding antibiotics all accumulate in the skeleton; herbimycin and protease inhibitors exhibit toxicity; estrogen analogues and inhibitors adversely affect hormone balance and sexual characteristics; and calcitonin and its relatives have yet to demonstrate meaningful effects.
It is thus clear that there is a significant need in the art for new compositions and methods by which to treat bone resorption and the many disease states that it causes or to which it contributes. The development of an anti-osteoclastic agent that exhibits low toxicity and has few side effects would represent a significant breakthrough, especially if such an agent was found to be readily available and could be administered orally.